title: Cytoprotective effects of taurine against toxicity induced by isoniazid and hydrazine in isolated rat hepatocytes.
abstract: Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no significant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine (200 μmol L(-1)) and N-acetylcysteine (200 μmol L(-1)) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Heidari
authors.forename: Hossein
authors.initials: H
authors.lastname: Babaei
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Eghbal
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D019610:Cytoprotection / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects*; D006834:Hydrazines / Q000633:toxicity*; D066298:In Vitro Techniques; D007538:Isoniazid / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*
chemical_list: D006834:Hydrazines; D017382:Reactive Oxygen Species; D013654:Taurine; C029424:hydrazine; D007538:Isoniazid; D000111:Acetylcysteine